Austin Leahy

Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis

BACKGROUND The formation of prostacyclin (PGI(2)), thromboxane (TX) A(2), and isoprostanes is markedly enhanced in atherosclerosis. We examined the relative contribution of cyclooxygenase (COX)-1 and -2 to the generation of these eicosanoids in patients with atherosclerosis. METHODS AND RESULTS The study population consisted of 42 patients with atherosclerosis who were undergoing surgical revascularization. COX-2 mRNA was detected in areas of atherosclerosis but not in normal blood vessel walls, and there was evidence of COX-1 induction. The use of immunohistochemical studies localized the COX-2 to proliferating vascular smooth muscle cells and macrophages. Twenty-four patients who did not previously receive aspirin were randomized to receive either no treatment or nimesulide at 24 hours before surgery and then for 3 days. Eighteen patients who were receiving aspirin were continued on a protocol of either aspirin alone or a combination of aspirin and nimesulide. Urinary levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha), metabolites of TXA(2) and PGI(2), respectively, were elevated in patients with atherosclerosis compared with normal subjects (3211+/-533 versus 679+/-63 pg/mg creatinine, P<0.001; 594+/-156 versus 130+/-22 pg/mg creatinine, P<0.05, respectively), as was the level of the isoprostane 8-iso-PGF(2alpha). Nimesulide reduced 2, 3-dinor-6-keto-PGF(1alpha) excretion by 46+/-5% (378.3+/-103 to 167+/-37 pg/mg creatinine, P<0.01) preoperatively and blunted the increase after surgery. Nimesulide had no significant effect on 11-dehydro-TXB(2) before (2678+/-694 to 2110+/-282 pg/mg creatinine) or after surgery. The levels of both products were lower in patients who were taking aspirin, and no further reduction was seen with the addition of nimesulide. None of the treatments influenced urinary 8-iso-PGF(2alpha) excretion. CONCLUSIONS Both COX-1 and -2 are expressed and contribute to the increase in PGI(2) in patients with atherosclerosis, whereas TXA(2) is generated by COX-1.

Concurrent colorectal malignancy and abdominal aortic aneurysm: a multicentre experience and review of the literature.

OBJECTIVES There is lack of consensus regarding concurrent vs. staged approaches, and the prioritisation of staged procedures in cases presenting with colorectal carcinoma (CRC) and abdominal aortic aneurysm (AAA) synchronously. We aim to present our experience, review the literature on this therapeutic dilemma and examine the role of endovascular aortic repair (EVAR). DESIGN, MATERIALS AND METHODS An observational study of the experience of two centres and a systematic review of the published literature. RESULTS Twenty-four patients were identified from the prospective databases of two tertiary referral centres between 2001 and 2006. Intervention for both malignancy and aneurysm was performed in 13 patients. In 10 patients, cancer resection was performed initially and was followed by open aneurysm repair (n=3) or EVAR (n=7). Two patients (AAA diameters: 7.0 and 8.0cm) underwent EVAR prior to colonic resection. One patient was selected for synchronous surgery. There were no interval AAA ruptures, graft infection or postoperative mortalities. Literature review identified 269 such cases; of these 101 were treated by combined surgery. In staged surgery, there were nine interval aneurysmal ruptures and one aortic graft infection. CONCLUSIONS In our experience, staged management can be undertaken, without interval aneurysmal rupture. EVAR has an evolving role in preventing delay in CRC management, in high-risk patients, and during combined intervention.

Ruptured abdominal aortic aneurysm — Can treatment costs and outcomes be predicted by using clinical or physiological parameters?

Mortality rates for patients undergoing surgery for ruptured abdominal aortic aneurysm (RAAA) remain high. The high cost of providing care for these patients mandates that proposed treatment protocols be evaluated for their cost-effectiveness. This study assessed costs related to outcome in different groups of patients with RAAA. From July 1987 to December 1993, 140 patients underwent emergency surgery for RAAA. Complete data on preoperative haemodynamic status, blood transfusion requirements, intensive care unit (ICU) stay and other hospital costs was available for 94 patients. Seventy-seven males (mean age 71.6(6)) and 17 females (mean age 77.2(6)) underwent surgery. Known risk factors including age (< or > 70 years), shock on admission (systolic blood pressure (BP) < or > 90 mm Hg), sex, and acute renal failure were analysed. For the purpose of comparison, costs (Pounds) were assessed by the ESRI (Economic and Social Research Institute of Ireland) based on 1992 prices. The overall survival rate was 48%: 53% among males and 24% among females (p < 0.05, Chi-squared test). In addition to having a significantly worse outcome than males, female patients with RAAA also had longer hospital and ICU stays and this was reflected in significantly greater expenditure. Similarly, male patients > 70 years old presenting with haemodynamic instability had significantly longer hospital and ICU stays than younger male patients. The average cost per RAAA survival (12,945 Pounds) in this series is not prohibitive, and the greater cost in high risk groups should not discourage intervention.

Asymptomatic carotid stenosis: A benign lesion?

Recent reports of the risk of asymptomatic carotid stenosis have been compromised by flawed patient selection or the performance of a large number of carotid endarterectomies during follow-up. We report the natural history of a randomly selected group of asymptomatic patients (n = 188; 114 males and 74 females) with documented carotid artery disease who were prospectively followed without intervention for up to 8 years. Risk factors included ischaemic heart disease in 17%, diabetes in 10%, hypertension in 46% and 88% were smokers. The degree of internal carotid stenosis was classified by duplex scanning and a total of 259 vessels had evidence of atherosclerosis. Study end-points included TIA, CVA and death. At mean follow-up of 4 years 3% of the 96 patients with internal carotid artery stenosis of less than 50% had died and 2% suffered a stroke. Six per cent of patients with a stenosis of 50-79% had died and 4% and 2% had suffered a CVA and TIA, respectively. In the 59 patients with greater than 80% stenosis 7% had suffered a TIA and an additional 7% a CVA, while 2% had died. None of the patients suffering a stroke had an antecedent TIA. Though the incidence of ischaemic events is significantly higher in patients with greater than 80% stenosis the incidence of unheralded stroke remains low. We therefore continue to recommend a conservative approach to the management of asymptomatic carotid stenosis.

An “all comers” policy for ruptured abdominal aortic aneurysms: how can results be improved?

OBJECTIVE To review our experience of a non-selective policy for the treatment of ruptured abdominal aortic aneurysm to see if the policy was justified, and to identify any preoperative risk factors that adversely influenced outcome. DESIGN Retrospective study. SETTING Teaching hospital, Republic of Ireland. SUBJECTS 258 patients admitted with abdominal aortic aneurysms between January 1982 and December 1993. INTERVENTIONS Definitive surgical treatment. MAIN OUTCOME MEASURES Morbidity, mortality, and risk factors. RESULTS In-hospital mortality for all patients was 43% (110/258). Overall, women did worse than men (28/44, 64%, died, compared with 96/214, 45%, p=0.03). The mortality among patients over the age of 80 (23/45, 51%) was not significantly different from that among younger patients (97/202, 48%). Blood pressure, platelet count, and haemoglobin concentration were all significantly lower preoperatively among those who died (p < 0.05). CONCLUSIONS Age alone cannot be used to justify witholding definitive surgical treatment. Treatment should be aimed towards reversing haematological and haemodynamic abnormalities preoperatively to try to improve outcome.

Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status.

INTRODUCTION Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)/RANKL/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking. MATERIALS AND METHODS 4 groups of patients were recruited - 26 with PAD and DM, 35 with DM alone, 22 with PAD alone, and 21 healthy individuals. Serum OPG, RANKL, TRAIL, hsCRP and IL-6 were measured using commercial ELISA assays. Presence and severity of PAD was defined using ankle brachial index (ABI). RESULTS Serum OPG (7.4±0.3 vs.5.8±0.2 pmol/l, p<0.0001), TRAIL (95.5±5.2 ng/ml vs. 76.2±4.4 ng/ml, p=0.006), hsCRP (2.6±0.3 vs. 1.8±0.3 mg/l, p=0.048), and IL-6 (4.1±0.4 vs. 2.9±0.4 pg/ml, p=0.06) were higher in patients with PAD. There was no difference in RANKL. Only OPG was significantly higher in PAD and DM (7.2±0.3 pmol/l) and PAD alone (7.7±0.4 pmol/l) compared to DM only (5.8±0.3 pmol/l) and healthy controls (5.6±0.4 pmol/l), p<0.01, but OPG was no higher in those with DM plus PAD versus those with PAD alone (p<0.3). Only OPG was associated with PAD severity, correlating negatively with ABI (r=-0.26, p=0.03), independent of age, gender, glycaemic status, hsCRP and IL-6. CONCLUSIONS PAD is associated with higher serum OPG, regardless of the co-existence of DM. This finding, in addition to its correlation with severity of PAD, suggests that OPG may be a novel marker for the presence and severity of PAD, possibly by reflecting the degree of underlying vascular calcification.

Acute Limb Ischemia in Cancer Patients: Should We Surgically Intervene?

BACKGROUND Cancer patients have an increased risk of venous thromboembolic events. Certain chemotherapeutic agents have also been associated with the development of thrombosis. Reported cases of acute arterial ischemic episodes in cancer patients are rare. METHODS Patients who underwent surgery for acute limb ischemia associated with malignancy in a university teaching hospital over a 10-year period were identified. Patient demographics, cancer type, chemotherapy use, site of thromboembolism, treatment and outcome were recorded. RESULTS Four hundred nineteen patients underwent surgical intervention for acute arterial ischemia, 16 of these patients (3.8%) had associated cancer. Commonest cancer sites were the urogenital tract (n = 5) and the lungs (n = 5). Eight patients (50%) had been recently diagnosed with cancer, and four (25%) of these cancers were incidental findings after presentation with acute limb ischemia. Four patients (25%) developed acute ischemia during chemotherapy. The superficial femoral artery was the most frequent site of occlusion (50%), followed by the brachial (18%) and popliteal (12%) arteries. All patients underwent thromboembolectomy, but two (12%) patients subsequently required a bypass procedure. Six patients (37%) had limb loss, and in-patient mortality was 12%. Histology revealed that all occlusions were due to thromboembolism, with no tumor cells identified. At follow-up, 44% of patients were found to be alive after 1 year. CONCLUSION Cancer and chemotherapy can predispose patients to acute arterial ischemia. Unlike other reports that view this finding as a preterminal event most appropriately treated by palliative measures, in this series, early diagnosis and surgical intervention enabled limb salvage and patient survival.

Arteriovenous fistula in dialysis patients: Factors implicated in early and late AVF maturation failure

Increasing numbers of patients are being diagnosed with end-stage renal disease (ESRD), and the demand for on haemodialysis (HD) is rising. Arteriovenous fistulae (AVFs) remain the best conduit for adequate HD, with fewer complications associated with long-term use compared to bypass grafts and central venous catheters. However, it is known that many newly formed fistulae do not mature to provide useful HD access. The paper provides a narrative overview of factors influencing the process of AVF maturation failure.

Laparoscopic cholecystectomy in the scarred abdomen

SummaryLaparoscopic cholecystectomy is rapidly becoming the definitive method for treating symptomatic gallbladder stones. Previous upper abdominal surgery is a relative contraindication to this technique. We describe a method for safely placing the trocars in a scarred abdomen, thus facilitating laparoscopic cholecystectomy in a wider group of patients.

Duplex Scanning for Noninvasive Assessment of Both Carotid Luminal Diameter and Atheromatous Plaque Morphology

The value of Duplex scanning in 50 consecutive patients with symptomatic carotid stenosis was evaluated. Compared with contrast arteriography, the sensitivity of Duplex scanning, for a greater than 50% internal carotid diameter reduction, was 90% (66/73) with a specificity of 96% (26/27). The overall agreement between Duplex and contrast arteriography as measured by the Kappa value was K = 0.561. One of the 13 arteries felt to be occluded on Duplex scanning was radiologically found to be patent. Excluding the six normal and 13 occluded arteries, 81 carotid plaques were defined as either heterogeneous, suggestive of intraplaque hemorrhage or as homogeneous. Twenty-four of the 32 asymptomatic cerebral hemispheres were associated with ipsilateral homogeneous plaques, while 30 of the 49 symptomatic hemispheres had heterogeneous plaques in the ipsilateral carotid, (p less than 0.001). This study confirms the accuracy of duplex scanning in detecting internal carotid stenosis as well as in identifying plaques which are morphologically heterogeneous and more likely to be associated with ipsilateral cerebral hemispheric symptoms.